We are going to investigate some basic problems in protein and enzyme chemistry using acetylcholinesterase and alkaline phosphatase. These problems include the mechanism of substrate inhibition, non-competitive inhibition, fluoride and arsenite inhibition, acceleration of reactions and secondary binding sites with the enzyme acetylcholinesterase. The study will involve measurements of the acetylenzyme intermediate and a theoretical and experimental investigation of electrostatic effects. The structure of the molecular forms of acetylcholineresterase from different sources will be studied to see if there is a common pattern of quaternary structure. We will try to identify and characterize muscarinic receptors in live neutrophils by direct binding of [ 3H]QNB. To do this we will have to overcome the permeable amine effect with suitable compounds. The mechanism of substrate activation and the question of one site activity will be studied with alkaline phosphatase as well as the kinetic details of the catalytic mechanism. The role of metal ions will be studied. The mechanism of rate enhancement by phosphate acceptors will be explored.